[ CAS No. 62400-75-3 ] {[proInfo.proName]}

Name: 62400-75-3|5-(Hydroxymethyl)pyrrolidin-2-one|95%
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Quality Control of [ 62400-75-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 62400-75-3 ]

Product Details of [ 62400-75-3 ]

CAS No. :	62400-75-3	MDL No. :	MFCD06661931
Formula :	C₅H₉NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HOBJEFOCIRXQKH-UHFFFAOYSA-N
M.W :	115.13	Pubchem ID :	558359
Synonyms :

Calculated chemistry of [ 62400-75-3 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.8
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	32.11
TPSA :	49.33 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.82 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.85
Log Po/w (XLOGP3) :	-1.15
Log Po/w (WLOGP) :	-1.12
Log Po/w (MLOGP) :	-0.78
Log Po/w (SILICOS-IT) :	0.37
Consensus Log Po/w :	-0.37

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.24
Solubility :	199.0 mg/ml ; 1.72 mol/l
Class :	Highly soluble
Log S (Ali) :	0.61
Solubility :	465.0 mg/ml ; 4.04 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.47
Solubility :	38.7 mg/ml ; 0.337 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

Safety of [ 62400-75-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 62400-75-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 62400-75-3 ]
Downstream synthetic route of [ 62400-75-3 ]

[ 62400-75-3 ] Synthesis Path-Upstream 1~10

1
[ 4931-66-2 ]
[ 62400-75-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium tetrahydroborate In methanol at 0 - 20℃; for 2 h; Inert atmosphere	To a stirred solution of methyl 5-oxopyrrolidine-2-carboxylate (9 g, 62.93 mmol) in MeOH (150 mL) under an argon atmosphere was added sodium borohydride (3.6 g, 95.2 mmol) at 0 ^oC. The reaction mixture was warmed to room temperature and stirred for 2 h. After consumption of starting material (monitored by TLC), the reaction mixture was quenched with concentrated HCl at 0 ^oC, filtered, and washed with MeOH (2 x 50 mL). The filtrate was concentrated in vacuo. The crude material was purified by column chromatography using 10percent MeOH: CH₂Cl₂ to afford 5-(hydroxymethyl) pyrrolidin-2-one (6 g, 83percent) as a colorless oil. LCMS: 116 (M+1); (column; X-Select CSH C-18 (50 × 3.0 mm, 3.5 µm); RT 0.44 min 5mM NH₄OAc in water: ACN; 0.80 mL/min); TLC: 10percent MeOH/ CH₂Cl₂ (R_f: 0.3).
83%	at 0 - 20℃; for 2 h; Inert atmosphere	Synthesis of 5-(hydroxymethyl) pyrrolidin-2-one To a stirred solution of methyl 5-oxopyrrolidine-2-carboxylate (9 g, 62.93 mmol) in MeOH (150 mL) under an argon atmosphere was added sodium borohydride (3.6 g, 95.2 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 2 h. After consumption of starting material (monitored by TLC), the reaction mixture was quenched with concentrated HCl at 0° C., filtered, and washed with MeOH (250 mL). The filtrate was concentrated in vacuo. The crude material was purified by column chromatography using 10percent MeOH: CH₂Cl₂ to afford 5-(hydroxymethyl) pyrrolidin-2-one (6 g, 83percent) as a colorless oil. LCMS: 116 (M+1); (column; X-Select CSH C-18 (503.0 mm, 3.5 μm); RT 0.44 min 5 mM NH₄OAc in water: ACN; 0.80 mL/min); TLC: 10percent MeOH/CH₂Cl₂ (R_f: 0.3).

Reference： [1] Patent: WO2015/109109, 2015, A1, . Location in patent: Paragraph 1239
[2] Patent: US2017/44182, 2017, A1, . Location in patent: Paragraph 1804

2
[ 66183-71-9 ]
[ 62400-75-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	at 0 - 20℃; for 6 h;	NaBH₄ (1.2 g, 30.0 mmol) was added slowly to a solution of J1 (8.0 g, 50.0 mmol) in ethanol (60 ml_) at 0 °C portionwise. The reaction mixture was allowed to stir at room temperature for 6 h. The mixture was quenched with concentrated HCI and the precipitated solid was filtered and purified by column chromatography on 100 - 200 silica gel with 8percent methanol in DCM as eluent to give pure J2 (4.7 g, 80percent) as pale yellow thick liquid. R_f: 0.1 (20percent MeOH in DCM, KMn0₄ active). ¹H NMR (400 MHz, cf₆-DMSO) δ 1 .65 - 1.78 (m, 1 H); 1.96 - 2.15 (m, 3H); 3.25 (m, 2H); 3.46 (m, 1 H); 3.92 (br. s., 1 H); 7.58 (br. s., 1 H).

Reference： [1] Patent: WO2015/181676, 2015, A1, . Location in patent: Page/Page column 164

3
[ 1159991-66-8 ]
[ 62400-75-3 ]

Reference： [1] Organic Letters, 2009, vol. 11, # 11, p. 2305 - 2307

4
[ 124-63-0 ]
[ 98-79-3 ]
[ 62400-75-3 ]

Reference： [1] Patent: US6509359, 2003, B1,

5
[ 5831-75-4 ]
[ 62400-75-3 ]

Reference： [1] Journal of Organic Chemistry, 1988, vol. 53, # 17, p. 4006 - 4014

6
[ 591-80-0 ]
[ 62400-75-3 ]

Reference： [1] Journal of Organic Chemistry, 1988, vol. 53, # 17, p. 4006 - 4014

7
[ 6852-94-4 ]
[ 62400-75-3 ]

Reference： [1] Journal of Organic Chemistry, 1988, vol. 53, # 17, p. 4006 - 4014

8
[ 39716-58-0 ]
[ 62400-75-3 ]

Reference： [1] Journal of Organic Chemistry, 1988, vol. 53, # 17, p. 4006 - 4014

9
[ 100556-54-5 ]
[ 62400-75-3 ]

Reference： [1] Journal of Organic Chemistry, 1988, vol. 53, # 17, p. 4006 - 4014

10
[ 149-87-1 ]
[ 62400-75-3 ]

Reference： [1] Patent: WO2015/109109, 2015, A1,
[2] Patent: WO2015/181676, 2015, A1,
[3] Patent: US2017/44182, 2017, A1,

[ 62400-75-3 ] Synthesis Path-Downstream 1~86

1
[ 62400-75-3 ]
5-(3,5-dinitro-benzoyloximethyl)-pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1938,vol. 60,p. 402,406

2
[ 62400-75-3 ]
[ 20873-93-2 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 851

3
[ 108-24-7 ]
[ 62400-75-3 ]
[ 60216-38-8 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

4
[ 100-52-7 ]
[ 62400-75-3 ]
[ 103201-79-2 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 1533 - 1536

5
[ 5831-75-4 ]
[ 62400-75-3 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

6
[ 123-91-1 ]
[ 62400-75-3 ]
copper oxide-chromium oxide [ No CAS ]
[ 20873-93-2 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 851

Yield	Reaction Conditions	Operation in experiment
		The compounds of formula (VII) that are particularly preferred are chosen from: ... 3-methyl-2-pyrrolidone 5-methyl-2-pyrrolidone 5-(hydroxymethyl)-2-pyrrolidinone 5-oxopyrrolidine-3-carboxylic acid ...

8
[ 123-91-1 ]
[ 4931-68-4 ]
copper oxide-chromium oxide [ No CAS ]
[ 62400-75-3 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 851

9
(+-)-5-oxo-pyrrolidine-2-carboxylic acid butyl ester [ No CAS ]
[ 62400-75-3 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 851

10
(+-)-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester [ No CAS ]
[ 62400-75-3 ]

Reference： [1]Journal of the American Chemical Society,1948,vol. 70,p. 3121
[2]Journal of the American Chemical Society,1938,vol. 60,p. 402,406

11
[ 1871-57-4 ]
[ 62400-75-3 ]
(S)-4-Methylene-hexahydro-pyrrolo[2,1-c][1,4]oxazepin-7-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 631 - 633

12
[ 13735-81-4 ]
[ 62400-75-3 ]
5-(2-oxo-2-phenylethyl)-2-pyrrolidinone [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334
[2]Tetrahedron Letters,2004,vol. 45,p. 1559 - 1563

13
[ 62400-75-3 ]
[ 762-72-1 ]
[ 82259-09-4 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334
[2]Tetrahedron Letters,2004,vol. 45,p. 1559 - 1563

14
[ 62400-75-3 ]
[ 202931-56-4 ]
C₂₂H₂₃N₅O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1367 - 1383

15
5-hydroxymethyl-1-trimethylsilanyl-pyrrolidin-2-one [ No CAS ]
[ 62400-75-3 ]

Reference： [1]Synthesis,2006,p. 1807 - 1810

16
[ 18388-03-9 ]
[ 62400-75-3 ]
5-[(2-chloromethyl)-2-propenyl]-2-pyrrolidinone [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334

17
[ 18295-80-2 ]
[ 62400-75-3 ]
(5SR,1'SR)-5-(1-chloro-2-methyl-2-propenyl)-2-pyrrolidinone [ No CAS ]
(5SR,1'RS)-5-(1-chloro-2-methyl-2-propenyl)-2-pyrrolidinone [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334

18
[ 62400-75-3 ]
[ 132279-21-1 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334

19
[ 62400-75-3 ]
[ 118311-90-3 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334
[2]Tetrahedron Letters,2004,vol. 45,p. 1559 - 1563

20
[ 62400-75-3 ]
[ 178671-86-8 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 325 - 334

21
[ 62400-75-3 ]
(S)-Tetrahydro-pyrrolo[2,1-c][1,4]oxazepine-4,7-dione [ No CAS ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 631 - 633

22
[ 591-80-0 ]
[ 62400-75-3 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

23
[ 6852-94-4 ]
[ 62400-75-3 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

24
[ 39716-58-0 ]
[ 62400-75-3 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

25
[ 100556-54-5 ]
[ 62400-75-3 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4006 - 4014

26
[ 62400-75-3 ]
[ 108827-55-0 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 1533 - 1536

27
[ 262439-88-3 ]
[ 62400-75-3 ]
[ 262439-99-6 ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine;	Example 14 [(2S)-5-Oxotetrahydro-1H-2-pyrrolyl]methyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate Phenyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate (30 mg, 0.065 mmol) was mixed with (5S)-5-(hydroxymethyl)tetrahydro-1H-2-pyrrolone (0.05 mL) in pyridine (0.5 mL). The reaction mixture was heated at 100 C. overnight. The solvent was removed and the residue was purified by preparative reverse phase LC/MS to give [(2S)-5-oxotetrahydro-1H-2-pyrrolyl]methyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate (10 mg, 0.021 mmol). 1H NMR (CDCl-d) delta1.90 (m, 1H), 2.06(m, 4H), 2.34 (m, 1H), 2.41 (m, 2H), 3.64 (m, 2H), 3.94 (s, 3H), 4.04(m, 2H), 4.14 (m, 2H), 4.98 (m, 1H), 5.33 (m, 3H), 6.10(s, 1H), 6.98 (s, 1H), 7.04 (s, 1H), 7.09 (m, 1H), 7.31(s, 1H), 8.11 (bs, 1H), 8.32 (s, 1H). LC/MS: MH+481.
	In pyridine;	Example 254 [(2S)-5-Oxotetrahydro-1H-2-pyrrolyl]methyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate Phenyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate (30 mg, 0.065 mmol) was mixed with (5S)-5-(hydroxymethyl)tetrahydro-1H-2-pyrrolone (0.05 mL) in pyridine (0.5 mL). The reaction mixture was heated at 100 C. overnight. The solvent was removed and the residue was purified by preparative reverse phase LC/MS to give [(2S)-5-oxotetrahydro-1H-2-pyrrolyl]methyl N-[4-(4-amino-7-tetrahydro-2H-4-pyranyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate (10 mg, 0.021 mmol). 1H NMR (CDCl-d) delta1.90 (m, 1H), 2.06(m, 4H), 2.34 (m, 1H), 2.41 (m, 2H), 3.64 (m, 2H), 3.94 (s, 3H), 4.04(m, 2H), 4.14 (m, 2H), 4.98 (m, 1H), 5.33 (m, 3H), 6.10(s, 1H), 6.98 (s, 1H), 7.04 (s, 1H), 7.09 (m, 1H), 7.31(s, 1H), 8.11 (bs, 1H), 8.32 (s, 1H). LC/MS: MH+481.

Reference： [1]Patent: US2003/153752,2003,A1
[2]Patent: US2003/153752,2003,A1

28
[ 124-63-0 ]
[ 98-79-3 ]
[ 62400-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	Example 4 1-1-{2-[(Amino)(imino)methyl]amino}-4-carboxyphenyl}-5-(aminomethyl)pyrrolidin-2-one An ice cold solution of 5-(hydroxymethyl)pyrrolidin-2-one (1.5 g, 13 mmol) prepared from 2-pyrrolidone-5-carboxylic acid (Valesinas et al., J. Org. Chem. 1992, 57, 2156-2160) in 20 mL of dichloromethane was treated with triethylamine (2.4 g, 23.5 mmol) and methylsulfonyl chloride (2.2 g, 19 mmol). The resulting solution was stirred at room temperature for 18 h. The reaction mixture was filtered to remove triethylamine hydrochloride and the filtrate was evaporated under reduced pressure.

Reference： [1]Patent: US6509359,2003,B1

29
potassium hexamethyl disilazane [ No CAS ]
[ 103667-54-5 ]
(3R-cis)-6-(2-cyclohexenyl)tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazole [ No CAS ]
[ 1521-51-3 ]
[ 62400-75-3 ]
(trans)-4-cyclohexyl-L-proline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium chloride; In tetrahydrofuran;	EXAMPLE 3 Alternative Process for Preparing (trans)-4-Cyclohexyl-L-proline (trans)-4-Cyclohexyl-L-proline was prepared from 5-hydroxymethyl-2-pyrrolidone using the proceduce described in Example 1, but substituting the following methodology for preparing (2S-trans)-4-cyclohexyl-2-pyrrolidinemethanol from (R)-tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one: Potassium hexamethyl disilazane (7.6 ml, 0.656 molar) was added to a suspension of lithium chloride (0.21 g) in dry tetrahydrofuran (10 ml) at -30 C. and stirred for 10 minutes, whereupon all the solids went into solution. A solution of (R)-tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one (1.0 g) in tetrahydrofuran (10 ml) was added and stirred for 30 minutes at -30 C. 3-Bromocyclohexene (0.9 ml) was added and the reaction mixture stirred for two hours at -20 C.; all the starting material was consumed. Extractive workup as in Example 2 furnished 1.40 g of (3R-cis)-6-(2-cyclohexenyl)tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazole which was used for the next step without any further purification. (2S-trans)-4-Cyclohexyl-2-pyrrolidinemethanol was prepared from (3R-cis)-6-(2-cyclohexenyl)tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazole using the methodology described in Example 2.

Reference： [1]Patent: US4588819,1986,A

30
[ 103667-54-5 ]
[ 1521-51-3 ]
[ 62400-75-3 ]
(trans)-4-cyclohexyl-L-proline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; n-butyllithium; diisopropylamine; In tetrahydrofuran; water; ethyl acetate;	EXAMPLE 2 Alternative process for preparing (trans)-4-cyclohexyl-L-proline (trans)-4-Cyclohexyl-L-proline was prepared from 5-hydroxymethyl-2-pyrrolidone using the procedure described in Example 1, but substituting the following methodology for preparing (2S-trans)-4-cyclohexyl-2-pyrrolidinemethanol from (R)-tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one: Diisopropylamine (12.9 ml) in dry tetrahydrofuran (250 ml) was cooled to -20 C. and n-butyllithium (37.2 ml, 2.73 molar) was added with stirring, keeping the temperature at about -20 C. (R)-Tetrahydro-3-phenyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one (18.7 g) in 50 ml of tetrahydrofuran was added to the solution at -78 C. and stirred for 30 minutes. 3-Bromocyclohexene (15.3 ml) was added as a neat solution at -78 C. and the temperature was brought to -20 C. and kept at that temperature for 2.5 hours. The reaction mixture was poured into crushed ice and water (about 300 ml), saturated with sodium chloride and extracted using ethyl acetate (3100 ml). The combined organic phase was washed with ice cold 2% aqueous hydrochloric acid (250 ml), water (250 ml) and brine (150 ml) and dried over sodium sulfate.

Reference： [1]Patent: US4588819,1986,A

31
[ 62400-75-3 ]
(7aR)-3,3-dimethyltetrahydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With Hg; toluene-4-sulfonic acid; In acetone; benzene;	Method II A mixture of 5-hydroxymethyl-2-pyrrolidone (0.4 g), acetone (5 ml) and p-toluenesulfonic acid (ca. 10 mg) was refluxed in 20 ml of benzene for 20 hours with a Dean-Stark water separator. After working up the reaction mixture, distillation (boiling point 70-75 C. at 0.5 mm of Hg) yielded 0.2 g or (R)-tetrahydro-3,3-dimethyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one as an oil.

Reference： [1]Patent: US4588819,1986,A

32
2-Dimethoxypropene [ No CAS ]
[ 62400-75-3 ]
(7aR)-3,3-dimethyltetrahydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; copper(II)bromide;	Method III A solution of 5-hydroxymethyl-2-pyrrolidone (3.0 g) in 100 ml of dichloromethane was cooled in an ice bath and powdered cupric bromide (0.1 g) was added. 2-Dimethoxypropene (2.0 g) in 10 ml of dichloromethane was added dropwise and after the addition, the cooling bath was removed and the reaction mixture stirred at room temperature for 1 hour and at reflux for 3 hours. Extractive work up followed by distillation yielded 2.8 g of (R)-tetrahydro-3,3-dimethyl-3H,5H-pyrrolo[1,2-c]oxazol-5-one as an oil.

Reference： [1]Patent: US4588819,1986,A

33
[ 616-45-5 ]
2-chloro-1,1,-trifluorotriethylamine [ No CAS ]
[ 62400-75-3 ]
4-fluoromethyl-4-amino-butyric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; hydrogenchloride; acetonitrile;	EXAMPLE 5 4-Amino-4-fluoromethylbutyric acid To a solution of 0.8 g (6.2 mmole) of 5-hydroxymethyl-2-pyrrolidone in a mixture of 20 ml of tetrahydrofuran and acetonitrile is added a solution of 1.2 g (6.4 mmole) of 2-chloro-1,1,-trifluorotriethylamine in 10 ml of tetrahydrofuran during 1/2 hour. The reaction mixture is allowed to stand at about 25 C. for 15 hours after which the solution is washed with water, potassium hydroxide until neutral, water and then dried over magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure leaving a residue which is distilled under high vacuum to afford 5-fluoromethyl-2-pyrrolidone. The pyrrolidone (500 mg) is heated in 20 ml of 6 N hydrochloric acid at reflux for 12 hours after which the solution is concentrated under vacuo and the residue passed through an Amberlite column IR 120 H+. Elution with 1 M ammonium hydroxide affords 4-amino-4-fluoromethylbutyric acid which is recrystallized from water/acetone.

Reference： [1]Patent: US4326071,1982,A

34
[ 62400-75-3 ]
[ 62400-90-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	With Dess-Martin periodane; In dichloromethane; at 20℃; for 1h;Inert atmosphere; Cooling with ice;	Under nitrogen protection,The compound <strong>[62400-75-3]5-(hydroxymethyl)pyrrolidin-2-one</strong> 21a (1.15 g, 10.0 mmol) was dissolved in dichloromethane (50 mL).DMP (5.1 g, 12.0 mmol) was added portionwise in an ice water bath, and the mixture was allowed to react to room temperature for 1 hour.Filtration, the filtrate was washed with saturated sodium sulfite solution, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography.To give the title compound 21b (0.8g, 7.1mmol), 71% yield.
	With pyridinium chlorochromate; In dichloromethane; acetonitrile;	(A) To a suspension of 15 mmole of pyridinium chlorochromate in 20 ml of methylene chloride is rapidly added at 25 C. a suspension of 10 mmole of 5-hydroxymethyl-2-pyrrolidone in 10 ml of acetonitrile. The mixture is stirred for 10 hours at 25 C. then diluted with diethyl ether. Filtration of the organic phase through florisil and concentration of the solvent at reduced pressure affords 5-formyl-2-pyrrolidone.

Reference： [1]Patent: CN109897011,2019,A .Location in patent: Paragraph 0582-0586
[2]Patent: US4326071,1982,A

35
[ 109-92-2 ]
[ 62400-75-3 ]
[ 67040-46-4 ]

Yield	Reaction Conditions	Operation in experiment
	With trichloroacetic acid; In chloroform;	(1) 4 g of dl-5-hydroxymethyl-2-pyrrolidone are dissolved in 20 ml of chloroform, and 0.1 g of trichloroacetic acid and 16 ml of vinylethylether are added thereto. The solution is stirred at room temperature for 4 hours. After the reaction, the solution is cooled with ice-water, and washed with an aqueous sodium bicarbonate solution. The washings is extracted with chloroform. Then, the reaction solution and chloroform extract are combined, and the combined mixture is washed with water saturated with ammonium sulfate, dried and evaporated to remove solvent. The residue thus obtained is distilled under reduced pressure. dl-5-[1-(Ethoxy)ethoxy-methyl]-2-pyrrolidone is obtained as pale yellow oil. Yield: 6.45 g. B.p. 137-138 C./1.5 mmHg
	With trichloroacetic acid;	(1) 17 g of l-5-hydroxymethyl-2-pyrrolidone, 0.43 g of trichloroacetic acid and 71 ml of vinylethylether are treated in the same manner as described in Example 2-(1). l-5-[1-(Ethoxy)ethoxymethyl]-2-pyrrolidone is obtained as pale yellow oil. Yield: 24.5 g B.p. 152-154 C./4 mmHg [alpha]D25 -22.6(C = 2, ethanol)
	With trichloroacetic acid;	(1) 3.65 g of d-5-hydroxymethyl-2-pyrrolidone, 0.1 g of trichloroacetic acid and 16 ml of vinylethylether are treated in the same manner as described in Example 2-(1). d-5-[1-(Ethoxy)ethoxymethyl]-2-pyrrolidone is obtained as pale yellow oil. Yield: 5.45 g B.p. 119-121 C./0.2 mmHg [alpha]D24.5 +20.8(C = 2, ethanol)

Reference： [1]Patent: US4113873,1978,A
[2]Patent: US4113873,1978,A
[3]Patent: US4113873,1978,A

36
[ 98491-29-3 ]
[ 62400-75-3 ]
[ 838872-71-2 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 2330 - 2344

37
[ 1159991-66-8 ]
[ 62400-75-3 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 2305 - 2307

38
[ 58479-61-1 ]
[ 62400-75-3 ]
[ 1309077-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; dmap; In dichloromethane; at 20℃;Cooling with ice;	Step (i): Preparation of 5-(tert-ButyldiphenylsilanyIoxymethyI)pyrrolidin-2-oneTo an ice cold solution of 5-Hydroxymethylpyrrolidin-2-one (5 grams, 43.4 mmol) in dichloromethane (174 ttiL) was added imidazole (6.5 grams, 95.5 mmol), 4- dimethylaminopyridine (530 mg, 4.3 mmol) followed by tert-butyldiphenylsilyl chloride (12.53 grams, 45.57 mmol). The reaction mixture was gradually warmed to room temperature and upon completion of 2 hours, diluted with dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain title compound of 15.37 grams, as gummy liquid, which was taken up for the next reaction without further purification.-NMR (CDC ): 7.65-7.63 (m, 4H), 7.45-7.37 (m, 6H), 3.84-3.77 (m, 1H), 3.62 (dd, J = 3.9, 10.2 Hz, 1H), 3.50 (dd, J = 7.7, 10.2 Hz, 1H), 2.40-2.30 (m, 2H), 2.20-2.1 1 (m, 1H), 1.76-1.67 (m, 1H), 1.05 (s, 9H);Mass (m/z): 354 [M+H*].
	With 1H-imidazole; dmap; In dichloromethane; at 20℃; for 2h;Cooling with ice;	To an ice cold solution of <strong>[62400-75-3]5-hydroxymethylpyrrolidin-2-one</strong> (5 grams, 43.4 mmol) in dichloromethane (174 mL) was added imidazole (6.5 grams, 95.5 mmol), 4- dimethylaminopyridine (530 mg, 4.3 mmol) followed by tert-butyldiphenylsilyl chloride (12.53 grams, 45.57 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain title compound of 15.37 grams, as gummy liquid, which was taken up for the next reaction without further purification.-NuMu (CDC13): 7.65-7.63 (m, 4H), 7.45-7.37 (m, 6H), 3.84-3.77 (m, 1H), 3.62 (dd, J = 3.9, 10.2 Hz, 1H), 3.50 (dd, J = 7.7, 10.2 Hz, 1H), 2.40-2.30 (m, 2H), 2.20-2.11 (m, 1H), 1.76-1.67 (m, 1H), 1.05 (s, 9H);Mass (m/z): 354 [M+H*].
	With 1H-imidazole; dmap; In dichloromethane; at 20℃; for 2h;Cooling with ice;	Step (i): Preparation of 5-(tert-Butyldiphenylsilanyloxymethyl)pyrrolidin-2-one To an ice cold solution of <strong>[62400-75-3]5-hydroxymethylpyrrolidin-2-one</strong> (5 grams, 43.4 mmol) in dichloromethane (174 mL) was added imidazole (6.5 grams, 95.5 mmol), 4-dimethylaminopyridine (530 mg, 4.3 mmol) followed by tert-butyldiphenylsilyl chloride (12.53 grams, 45.57 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain title compound of 15.37 grams, as gummy liquid, which was taken up for the next reaction without further purification. 1H-NMR (CDCl3): 7.65-7.63 (m, 4H), 7.45-7.37 (m, 6H), 3.84-3.77 (m, 1H), 3.62 (dd, J=3.9, 10.2 Hz, 1H), 3.50 (dd, J=7.7, 10.2 Hz, 1H), 2.40-2.30 (m, 2H), 2.20-2.11 (m, 1H), 1.76-1.67 (m, 1H), 1.05 (s, 9H); Mass (m/z): 354 [M+H+].

15.37 g

With 1H-imidazole; dmap; In dichloromethane; at 20℃; for 2h;Cooling with ice;

To an ice cold solution of 5-Hydroxymethylpyrrolidin-2-one (5 grams, 43.4 mmol) in dichloromethane (174 mL) was added imidazole (6.5 grams, 95.5 mmol), 4-dimethylaminopyridine (530 mg, 4.3 mmol) followed by tert-butyldiphenylsilyl chloride (12.53 grams, 45.57 mmol). The reaction mixture was gradually warmed to room temperature and upon completion of 2 hours, diluted with dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain title compound of 15.37 grams, as gummy liquid, which was taken up for the next reaction without further purification. 1H-NMR (CDCl3): 7.65-7.63 (m, 4H), 7.45-7.37 (m, 6H), 3.84-3.77 (m, 1H), 3.62 (dd, J=3.9, 10.2 Hz, 1H), 3.50 (dd, J=7.7, 10.2 Hz, 1H), 2.40-2.30 (m, 2H), 2.20-2.11 (m, 1H), 1.76-1.67 (m, 1H), 1.05 (s, 9H); Mass (m/z): 354 [M+H+].

Reference： [1]Patent: WO2011/61751,2011,A1 .Location in patent: Page/Page column 20
[2]Patent: WO2011/80751,2011,A2 .Location in patent: Page/Page column 22
[3]Patent: US2012/322808,2012,A1 .Location in patent: Page/Page column 9
[4]Patent: US2013/72518,2013,A1 .Location in patent: Paragraph 0145-0147

39
[ 62400-75-3 ]
2-(tert-butyldiphenylsilanyloxymethyl)-5-oxo pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2013/72518,2013,A1

40
[ 62400-75-3 ]
[ 157979-33-4 ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2012/322808,2012,A1
[4]Patent: US2013/72518,2013,A1

41
[ 62400-75-3 ]
[ 157979-35-6 ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2012/322808,2012,A1
[4]Patent: US2013/72518,2013,A1

42
[ 62400-75-3 ]
2-(tert-butyldiphenylsilanyloxymethyl)-2,3-dihydropyrrole-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2012/322808,2012,A1
[4]Patent: US2013/72518,2013,A1

43
[ 62400-75-3 ]
[ 1309077-13-1 ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2012/322808,2012,A1
[4]Patent: US2013/72518,2013,A1

44
[ 62400-75-3 ]
[ 1309077-14-2 ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: WO2011/80751,2011,A2
[3]Patent: US2012/322808,2012,A1
[4]Patent: US2013/72518,2013,A1

45
[ 62400-75-3 ]
[ 1309077-15-3 ]

Reference： [1]Patent: WO2011/61751,2011,A1
[2]Patent: US2013/72518,2013,A1

46
[ 62400-75-3 ]
3-(pyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride [ No CAS ]

Reference： [1]Patent: WO2011/61751,2011,A1

47
[ 62400-75-3 ]
[ 1309076-31-0 ]

Reference： [1]Patent: WO2011/61751,2011,A1

48
[ 62400-75-3 ]
[ 1309077-06-2 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

49
[ 62400-75-3 ]
[ 1313814-82-2 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

50
[ 62400-75-3 ]
[ 1313816-82-8 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

51
[ 62400-75-3 ]
[ 1313816-83-9 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

52
[ 62400-75-3 ]
[ 1313816-89-5 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

53
[ 62400-75-3 ]
[ 1313816-92-0 ]

Reference： [1]Patent: WO2011/80751,2011,A2
[2]Patent: US2012/322808,2012,A1

54
[ 62400-75-3 ]
N-[2-(5-bromopyridin-3-yl)-2-azabicyclo[3.1.0]hex-3-ylmethyl]-dimethylamine hydrochloride [ No CAS ]

Reference： [1]Patent: WO2011/80751,2011,A2

55
[ 98-09-9 ]
[ 62400-75-3 ]
[ 1312454-15-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetone; at 20℃; for 3h;	Example 3.3a. Synthesis of (5-oxopyrrolidin-2-yl)methyl benzenesulfonateTo a stirred solution of <strong>[62400-75-3]5-(hydroxymethyl)pyrrolidin-2-one</strong> (1.0 g, 8.7 mmol) in acetone (80 mL) was added Et3N (1.8 g, 17.4mmol) and benzenesulfonyl chloride (3.1 g, 17.4 mmol). The mixture was stirred for 3 h at room temperature. Then the reaction mixture was filtered and concentrated, and the crude product was purified by columnchromatography to give the desired product. MS (ESI): 256 (MH+).

Reference： [1]Patent: WO2011/75699,2011,A2 .Location in patent: Page/Page column 127

56
[ 62400-75-3 ]
[ 1449794-26-6 ]

Reference： [1]Russian Chemical Bulletin,2012,vol. 61,p. 2096 - 2101
Izv. Akad. Nauk, Ser. Khim.,2012,p. 2079 - 2084,6

57
[ 62400-75-3 ]
[ 1449794-28-8 ]

Reference： [1]Russian Chemical Bulletin,2012,vol. 61,p. 2096 - 2101
Izv. Akad. Nauk, Ser. Khim.,2012,p. 2079 - 2084,6

58
[ 62400-75-3 ]
[ 1449794-16-4 ]

Reference： [1]Russian Chemical Bulletin,2012,vol. 61,p. 2096 - 2101
Izv. Akad. Nauk, Ser. Khim.,2012,p. 2079 - 2084,6

59
[ 62400-75-3 ]
[ 1449794-18-6 ]

Reference： [1]Russian Chemical Bulletin,2012,vol. 61,p. 2096 - 2101
Izv. Akad. Nauk, Ser. Khim.,2012,p. 2079 - 2084,6

60
[ 4931-66-2 ]
[ 62400-75-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 2h;Inert atmosphere;	To a stirred solution of methyl 5-oxopyrrolidine-2-carboxylate (9 g, 62.93 mmol) in MeOH (150 mL) under an argon atmosphere was added sodium borohydride (3.6 g, 95.2 mmol) at 0 oC. The reaction mixture was warmed to room temperature and stirred for 2 h. After consumption of starting material (monitored by TLC), the reaction mixture was quenched with concentrated HCl at 0 oC, filtered, and washed with MeOH (2 x 50 mL). The filtrate was concentrated in vacuo. The crude material was purified by column chromatography using 10% MeOH: CH2Cl2 to afford 5-(hydroxymethyl) pyrrolidin-2-one (6 g, 83%) as a colorless oil. LCMS: 116 (M+1); (column; X-Select CSH C-18 (50 × 3.0 mm, 3.5 mum); RT 0.44 min 5mM NH4OAc in water: ACN; 0.80 mL/min); TLC: 10% MeOH/ CH2Cl2 (Rf: 0.3).
83%	With methanol; sodium tetrahydroborate; at 0 - 20℃; for 2h;Inert atmosphere;	Synthesis of 5-(hydroxymethyl) pyrrolidin-2-one To a stirred solution of methyl 5-oxopyrrolidine-2-carboxylate (9 g, 62.93 mmol) in MeOH (150 mL) under an argon atmosphere was added sodium borohydride (3.6 g, 95.2 mmol) at 0 C. The reaction mixture was warmed to room temperature and stirred for 2 h. After consumption of starting material (monitored by TLC), the reaction mixture was quenched with concentrated HCl at 0 C., filtered, and washed with MeOH (250 mL). The filtrate was concentrated in vacuo. The crude material was purified by column chromatography using 10% MeOH: CH2Cl2 to afford 5-(hydroxymethyl) pyrrolidin-2-one (6 g, 83%) as a colorless oil. LCMS: 116 (M+1); (column; X-Select CSH C-18 (503.0 mm, 3.5 mum); RT 0.44 min 5 mM NH4OAc in water: ACN; 0.80 mL/min); TLC: 10% MeOH/CH2Cl2 (Rf: 0.3).

Reference： [1]Patent: WO2015/109109,2015,A1 .Location in patent: Paragraph 1239
[2]Patent: US2017/44182,2017,A1 .Location in patent: Paragraph 1804

61
[ 149-87-1 ]
[ 62400-75-3 ]

Reference： [1]Patent: WO2015/109109,2015,A1
[2]Patent: WO2015/181676,2015,A1
[3]Patent: US2017/44182,2017,A1

62
[ 62400-75-3 ]
(+)-2-((5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)amino)-6,6a,7,8-tetrahydro-9H-pyrimido[5,4-b]pyrrolo[1,2-d][1,4]oxazin-9-one [ No CAS ]
(-)-2-((5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)amino)-6,6a,7,8-tetrahydro-9H-pyrimido[5,4-b]pyrrolo[1,2-d][1,4]oxazin-9-one [ No CAS ]